tbuckley/cabot-search huggingface dataset:
Abstract 15554: Smooth Muscle Cells Specific Gene Inactivation of Lysyl Oxidase Reduces Atherosclerosis Burden and Plaque Calcification in Hyperlipidemic Mice
Authors: Filipe F Stoyell Conti, Miguel Rojas, Zachary Zigmond, Mohdahmar Rauf, Laisel Martinez, Roberto I Vazquez-Padron
Journal: Circulation (2022)

Aim: Dissect the mechanisms by which LOX increases atherogenesis and plaque calcification in hyperlipidemic mice. Methods: LOX conditional knockout [LOX f/f Myh11-CreER T2 ApoE -/- ] and control littermate [LOX wt/wt Myh11-CreER T2 ApoE -/- ] mice were injected with tamoxifen before high fat diet (HFD) feeding for atherosclerosis and calcification assessment and molecular analyses. Results: scRNA sequence showed full Lox gene inactivation in 72.5% of the aortic SMCs without any significant Loxl compensatory regulation. Gene deletion in SMCs decreased global arterial LOX deposition by ~3-fold in relation to control mice. Surprisingly, the loss of vascular LOX neither promoted aneurysm nor affected the aorta's stiffness. However, it reduced atherosclerosis burden (WT: 23±1 vs. KO: 13±2 %, p ≤0.01) and calcium deposition (11.8±3 versus 5±0.4%, p≤ 0.05) within the plaque after 16 weeks of high fat diet (HFD). Using bulk RNA sequencing, we further demonstrated that Lox gene inactivation leads to a marked decrease in Frizzled Related Protein-3 (FRZB) gene expression (127-fold and p≤0.0001), a biphasic modulator of the proatherogenic Wnt signaling that facilitates the association of β-catenin with TCF4 in the nucleus. The compromised FRZB /β-catenin/TCF4 signaling axis reduced the downstream production of Bone Morphogenetic Protein 2 (BMP2), which is responsible for the osteogenic transition of SMCs. Further scRNAseq analysis of atherosclerotic aortas from conditional KO and control mice also showed a reduction of BMP2 in SMCs. Interestingly, genetic inactivation of LOX increased the number of contractile SMCs (KO: 40 vs. WT: 7 %), characterized by the high expression of ACTA2 and TAGLN, in the aorta of HFD fed mice when compared to the control group. BAPN, an irreversible inhibitor of LOX activity, was not able to reduce BMP2 expression and protein levels nor reduce calcium deposition in vitro, suggesting that the pro-calcification effect of LOX is not activity dependent. Conclusions: Vascular gene inactivation of Lox protects mice against atherosclerosis by reducing β-catenin/TCF4/BMP2 proatherogenic signaling.
Abstract 248: Current Status Of In-hospital Cardiac Arrest And Issues Of Collecting Data Using The Latest In-hospital Utstein-style Reporting Templates
Authors: Yu Kanayama, Takeyuki Kiguchi, Chika Nishiyama, Takashi Morita
Journal: Circulation (2022)

[Background]: The outcome of in-hospital cardiac arrest has improved over the past decade, although the survival rate is still approximately 25%. The in-hospital Utstein-style reporting templates were international standard template for in-hospital cardiac arrest, with items to be substantially revised in 2019, with recommendations for standardization of records to allow objective comparisons. The aim of this study is to analyze the current status of in-hospital cardiac arrest in our hospital, and to clarify the issues in collecting the data using the in-hospital Utstein-style reporting templates. [Methods]: We collected the reports of 3 years in-hospital cardiac arrests occurred between April 2019 and March 2022 in our hospital. We described all reported items and their proportion (Patient, Pre-event, Cardiac arrest process, Post-resuscitation process, and Outcome), and calculated the missing rate of each item. [Results]: A total of 106 cases during the study period, and all reports were submitted by nurses. The median age was 74 years old (IQR: 64-81), 60.4% were male, 76.4% of cases were witnessed, chest compressions were 67.9%, and shock delivered were in 5.9%. The initial shockable rhythm was in 15.1% of cases (Table). Some items had missing data or invalid responses. Date and time of event, initial rhythm, the time of first shock delivered, and 30 days outcome had missing data (rate of missing 33%, 13.2%, 44.4%, and 80.7%, respectively), which were core items of the latest in-hospital Utstein-style reporting templates. Patient category, post-resuscitation process, reason for CPR stopped, and neurological outcome at 30 days were not measured. [Conclusions]: The high rate of missing data is considered that the nurses may not understand the meaning of the items, and suggested the need for education of nurses who submit reports.
Abstract 15645: Posterior Mediastinal Hematoma as a Rare Complication of Anti-Coagulation Use - A Case Report and Literature Review
Authors: verda arshad, Nataly Akbarshahi, Saad S Ahmad
Journal: Circulation (2022)

Introduction: Posterior mediastinal hematoma (PMH) is a rare complication of anti-coagulation (AC) use. We present a complex case of a patient with a sub-massive pulmonary embolism (PE) whose care was complicated by PMH causing airway obstruction following thrombectomy. Case: A 60-year-old male with a history of prostate cancer in remission presented after a syncopal event. On admission, he was afebrile, mildly tachycardic (100bpm), normotensive (135/91), with no oxygen requirement. Laboratory data showed high sensitivity troponin 244 ng/L and BNP 82 pg/ml. CTPA revealed a saddle PE with right heart strain (PESI score 100). He was initiated on anticoagulation and underwent successful mechanical thrombectomy using a Penumbra aspiration catheter. He had acute respiratory failure later that evening, necessitating intubation. Repeat CTPA showed increased clot burden and new onset PMH (Figure 1). Of note, his AC was continued due to clot burden. A repeat thrombectomy was performed using the FlowTriever System Device (Inari Medical, Irvine, CA). Despite this intervention, he continued to struggle with extubation, and a new stridor was noted. Bronchoscopy revealed external compression of proximal trachea correlating with the PMH location. He was deemed too high risk for evacuation of the PMH. Therefore, he underwent tracheostomy to bypass the area of compression. This subsequently allowed for successful extubation. Discussion: While thrombectomy can cause iatrogenic bleeding, no bleeding was seen on the post-procedure angiogram in our patient. Thus, these findings are attributed to PMH. PMH has been reported 6 times in literature (table 1), one associated with PE. Management options include hematoma evacuation or holding AC and performing serial follow up imaging. Our patient did not undergo evacuation of hematoma, and a tracheostomy was used instead to bypass the obstruction. This highlights the need to individualize management of these complex patients.
Abstract 15431: Engineered Nanovesicles With Microrna-126 Cargo Improve Cardiac Repair After Myocardial Infarction in a Rat Ischemia-Reperfusion Model
Authors: Sruti Bheri, Milton E Brown, Hyun-Ji Park, Jessica Hoffman, Michael E Davis
Journal: Circulation (2022)

Introduction: Ckit+ progenitor cells (CPCs) produce small extracellular vesicles (sEVs) which are pivotal for CPC-based cardiac repair after myocardial infarction (MI). sEVs encapsulate potent RNA cargo within a bilayer membrane which aids with sEV uptake. However, despite established benefits, sEV therapies are limited by inconsistent sEV release from cells and variable cargo encapsulation. Further, although synthetic sEV mimics allow cargo tunability, they suffer rapid clearance when administered. We have developed an sEV-like vesicle (ELV) which maintains an sEV-like membrane, important for efficient uptake, but allows cargo control like that of sEV-mimics. We hypothesize that ELVs with proangiogenic microRNA (miR) cargo improve cardiac repair in a rat ischemia-reperfusion (IR) model compared to sEVs and that this occurs in a dose-dependent manner. Methods: sEVs were isolated from CPC conditioned media via ultracentrifugation and sEV inherent cargo was depleted with sonication. ELVs with miR-126 cargo were synthesized from sEVs using square-wave electroporation and characterized. miR-126+ELVs and sEVs (at 5 μg/kg or 10 μg/kg) were administered intramyocardially to the failing left-ventricle (LV) of Sprague Dawley rats after 30-minute IR injury. Infarct size was quantified with TTC/Evans blue staining after 24 hours. LV global and segmental hemodynamic parameters were assessed at baseline, Day 7, 14, and 28. After 28 days, LV fibrosis, hypertrophy and vessel formation were assessed with picrosirius red, wheat germ agglutinin and isolectin staining, respectively. Results: miR-126+ELVs were of similar size and concentration to CPC-sEVs. Upon administration, all groups reduced infarct size 24 hours post-treatment compared to IR-only. Further, ELV groups improved global hemodynamic parameters compared to controls with a dose-dependent segmental response across the LV. Finally, miR-126+ELVs increased vessel density compared to sEVs. Conclusion: ELVs with an sEV-like membrane but tailored cargo allow for cardiac repair after MI in a rat IR model, with both global and regional hemodynamic improvements and tunable histological responses. This work highlights the scope of miR+ELV therapies for cardiac diseases even beyond MI.
Abstract 15627: Inferior Vena Cava Filter Strut Fracture and Migration to the Right Ventricle in Post-COVID Patient With Intractable Cough
Authors: Sachin Kumar, Muhammad M Furqan, Rhonda Miyasaka, Gautam Shah
Journal: Circulation (2022)

Background: Inferior vena cava (IVC) filter fracture and migration of the fractured strut is a rare but potentially dangerous complication. We report a case of fractured IVC strut migrated to the right ventricle (RV) in a patient who was evaluated for persistent cough. Clinical Case: A 69-year-old male presented to his primary care physician for the evaluation of intractable cough and shortness of breath. Past medical history was significant for recurrent unprovoked deep vein thromboses treated with an IVC filter 15 years ago. He had COVID19 infection six months prior to current presentation. A computed tomography (CT) scan of the chest was ordered to screen for underlying pulmonary disease. CT scan showed no pulmonary process, but revealed a linear radiopaque foreign body in the RV of the heart. His cough was considered to be a sequela of his prior COIVD19 infection. Decision-making: To better characterize this foreign body in RV, a transesophageal echocardiogram was performed. This showed a prominent linear echo density on the tricuspid valve chord in the RV. On careful review of the CT scan of the chest and comparison with prior CT scans, it was found that one of the IVC filter strut at 9 o’ clock position was missing. The ‘foreign body’ in the RV had the same size as the remaining struts of the IVC filter. Given that the patient did not have any symptoms or complications from the incidentally found fractured strut, decision was made to not retrieve it with a percutaneous or surgical intervention. Conclusion: Significant variations in the intra-abdominal pressure may contribute to metal fatigue potentially leading to IVC filter strut fracture and migration to the RV. This underscores the importance of timely removal of IVC filters. Uncomplicated migrated IVC filter struts may be left unretrieved and patients can be followed clinically.
Abstract 15507: The Role of Obesity in Covid-19 Pathogenesis and Inflammation
Authors: joshua M currey, Xuebin Qin, Robert Blair, Cecily Midkiff, Jay Rappaport, Jay Kolls, Franck Mauvais-Jarvis, Nicholas Maness
Journal: Circulation (2022)

SARS-CoV-2 has caused a global pandemic unseen for nearly a century. To date hundreds of millions of people have been diagnosed and millions more have died from COVID-19 disease; many of which are in groups with comorbidities. Obesity is associated with a 3.07 times higher risk of hospitalization and a 1.42 times higher risk of severe illness. However, our understanding of obesity-accelerated severity of COVID-19 is limited. To model the increased disease severity of obese individuals with COVID-19, we used a humanized ACE2 (hACE2) transgenic mouse model, in which hACE2 is under the cytokeratin-18 promoter (K18). Modeling the effects of obesity on COVID-19 in K18-hACE2 mice will help us better understand the mechanisms underlying obesity-accelerated severity of COVID-19 disease and inflammation. We have developed a study in which K18 hACE2 mice infected with SARS-CoV-2 were fed both a normal standard diet as well as a western high fat and carbohydrate diet that causes them to gain excess weight and become obese over a period of 3 months. K18-hACE2 obese mice lose a signifyingly more percentage body weight over both a 7 (acute) 14 day (long-term) period than normal diet fed mice do after infection with SARS-CoV-2. H&amp;E staining analysis of lung histological changes indicated a dramatic increase in inflammation in our K18 hACE2 obese mice infected with SARS-CoV-2 . Subgenomic qPCR and IHC staining was used to quantify virus (viral titer) which indicated that in both of our diet groups after infection did not have a significantly different SARS-CoV-2 viral load. No significant difference in the SARS-CoV-2 viral load was detected at either 7 or 14 dpi with SARS-CoV-2 . We further measured adipokines with an ELISA on two of the most notable adipokines: leptin and adiponectin. Levels of leptin were significantly higher in our obese K18-hACE2 mice but not in our normal mice after infection. There was no difference however in the levels of adiponectin. Obese K18-hACE2 mice show a more severe COVID 19 phenotype than normal diet mice after infection and can be used to further study the underlying mechanism of how SARS-CoV-2 infection in obese individuals causes a more severe disease phenotype.
Abstract 15358: Comparative Performance of Recurrent Heart Failure Prediction Models: Incorporating Social Determinants and Applying Machine Learning
Authors: Aniruddha Deshpande, Alanna A Morris, Joyce C Ho, Shivani A Patel
Journal: Circulation (2022)

Introduction: Improving performance of predictive algorithms for 30-d readmission following heart failure (HF) hospitalization may enhance clinical management decisions. Applying novel data (social determinants of health; SDOH) and novel methods (machine learning) have been proposed. We compared performance to predict 30-d HF readmission using models with and without SDOH and under traditional and machine learning techniques. Hypothesis and Methods: We used data on 27,071 admissions within Emory Healthcare (mean age: 66 , 48% female, 51% black). We categorized 69 covariates as patient-level clinical (e.g., diastolic blood pressure), patient-level demographic (e.g. gender, age), and zip code SDOH (e.g. percent unemployed). Logistic regression under generalized linear model (GLM) and gradient boosted model (GBM) frameworks were applied to test all combinations of covariate sets. We evaluated performance using 5-fold cross-validation calculating area under the curve (AUC; discrimination) and mean absolute error (MAE; calibration) statistics. Results: 30-d readmission occurred in 17.7% of hospital admissions. Under GLM, model performance was similar across all covariate sets (AUCs .500 - .502). Under GBM, model performance measures were higher than GLM but similar across covariate sets (.500-.664). Notably, SDOH improved model discrimination (AUC .606 clinical only, AUC .664 clinical+SDOH) in the full dataset (“in-sample”) runs. Conclusions: Patient clinical data provided the richest information for prediction of HF readmission, with incremental gains through the addition of area SDOH data such as zip code level unemployment. Furthermore, these gains were only realized in GBM highlighting the marginal utility in flexible modeling methods. While non-clinical data sources can provide a rich understanding of the social mechanisms producing disease, their utility for clinical prediction may be outcome-specific.
Abstract 181: In-hospital Cardiac Arrest Debrief In A Pediatric Intensive Care Unit
Authors: Benny Joyner, Afsaneh Pirzadeh, Christen Seaman, Matthew Pizzuto
Journal: Circulation (2022)

Background: Debrief of in-hospital cardiac arrests (IHCA) has been shown to improve outcomes. There can be limited data available to quantitatively review a resuscitation, but careful analysis can provide insight for improvement. Methods: A standard process for debriefing all cardiac arrests was developed in our institution’s pediatric intensive care unit (PICU). Characteristics of the event were documented, and each arrest was independently reviewed by a lead arrest review investigator including telemetry data, chart review, and provider interviews when available. Data was stored in a secure redcap database. Results: From April 1, 2021 to March 31, 2022 there were n=25 IHCAs in 22 patients. Eighteen (72%) were classified as severe bradycardia with hypotension and/or poor perfusion; 6 (24%) were pulseless electrical activity; and 1 was unstable VT/VF. Two patients had a shockable rhythm during their arrest. The median arrest duration was 6 minutes with the longest duration being 104 minutes. Out of the 25 arrests, 18 (72%) had return of spontaneous circulation. Out of the 22 patients who had at least 1 arrest, 9 (41%) survived to hospital discharge and 12 (55%) died; 1 patient is still admitted. In addition to outcomes data, the debrief process led to many process improvements including the utility of a backboard (Figure 1A) and use of the respiratory rate tracing (thoracic impedance) in assessing compressions (Figure 1B). Discussion: IHCA in pediatric patients confers a significant risk of mortality and morbidity. Development of a comprehensive debrief process will help to identify areas for improvement in all facets of arrest care.
Abstract 199: Femoral Artery Doppler Ultrasound Blood Flow Patterns Predict Intrinsic Pulsatility In Cardiac Arrest Patients Receiving Active Chest Compressions
Authors: Daniel M Rolston, Alexander V Nello, Timmy Li, Daniel Jafari, Lance B Becker, Casey Owens, Ghania Haddad Essaihi, Allison L Cohen
Journal: Circulation (2022)

Introduction: Pulse detection requires chest compression interruption, which is associated with poor outcomes in cardiac arrest. Currently no modality can reliably identify return of spontaneous circulation with ongoing chest compressions. Hypothesis We hypothesized that patients with intrinsic pulsatility have anterograde dominant blood flow (ADF) on arterial Doppler ultrasound; whereas those with intrinsic pulselessness have bidirectional blood flow moving antero/retrograde during chest compression/decompression. Methods: We conducted a prospective, diagnostic accuracy study on a convenience sample of adult Emergency Department (ED) cardiac arrest patients with a femoral arterial line in place. Immediately prior to a pulse check, pulsed-wave Doppler ultrasound of the common femoral artery was performed during active chest compressions. Bidirectional flow was present when the anterograde flow waveform was equal in peak systolic velocity to the retrograde flow waveform. All other Doppler waveforms were ADF. A pulse was present when there was an arterial line waveform. Sensitivity, specificity, and accuracy of ADF versus bidirectional flow for predicting pulsatility was assessed. Results: We enrolled 42 patients and performed 104 pulse checks: a pulse was present for 73 (70.2%) and absent in 31 (29.8%). ADF was present in 82 (78.9%) and bidirectional flow was present in 22 (21.2%). Sensitivity of ADF for detecting a pulse was 95.9% (95% CI: 91.3%-100.0%). Specificity of bidirectional flow for detecting pulselessness was 61.3% (95% CI: 44.1-78.4%) and accuracy was 85.6% (95% CI: 77.3-91.7%). Patients with ADF have 36.9 times the odds of having an arterial line pulse compared with patients with bidirectional flow (OR: 36.9; 95% CI: 9.5-144.4). Conclusion: In ED cardiac arrest patients, ADF on Doppler ultrasound has high sensitivity for detecting an arterial line pulse. Further studies are needed to further evaluate this novel finding.
Abstract 190: Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) After Traumatic Brain Injury 
Authors: Kristen Nordham, Scott Ninokawa, Jacob Broome, Scott McCraney, John Simpson, Danielle Tatum, Olan Jackson-Weaver, Sharven Taghavi, PATRICK MCGREW, juan duchesne
Journal: Circulation (2022)

Aim: The effects of resuscitative endovascular balloon occlusion of the aorta (REBOA) on progression of traumatic brain injury (TBI) are unclear. Swine models have shown conflicting results, and human data is lacking. Two hypotheses largely prevail: increased mean arterial pressure caused by REBOA may improve cerebral perfusion, or conversely, cause cerebral edema due to elevated blood and intracranial pressure. This study aims to compare outcomes in patients with TBI treated with and without REBOA. Methods: A retrospective analysis compared blunt trauma patients with TBI treated with REBOA to those treated without. REBOA patients were selected from the Aortic Occlusion for Resuscitation in Trauma and Acute Care Surgery (AORTA) registry, and non-REBOA patients were selected from an institutional trauma registry. Patients with SBP &gt; 0mmHg at admission and at initiation of aortic occlusion were included. Patients requiring CPR at ED were excluded. Propensity score matching was performed using age, gender, ISS, AIS-Head, and admission SBP. Results: After matching, 106 REBOA patients and 106 non-REBOA patients remained for analysis. REBOA patients had significantly higher ISS, but there was no difference in AIS-Head, pre-hospital or ED GCS, ED SBP, or in-hospital mortality (Table). Despite longer hospital stays for REBOA patients, there was no difference in ICU length of stay or rate of discharge home between groups. Conclusion: REBOA was used in more severely injured patients, but was not associated with higher mortality rate. Despite longer hospital stays for REBOA patients, discharge GCS and rate of discharge home, both favorable patient-centered outcomes, were similar between groups. REBOA use should be considered for use in patients with non-compressible torso hemorrhage and concomitant TBI, as it here it did not increase mortality, and outcomes upon discharge are similar to patients treated without REBOA.